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Successful Transplantation of Photoreceptors into the Retina of an Adult Mouse Model of Human Retinitis Pigmentosa

¹ Div of Molecular Therapy, Institute of Ophthalmology, London, United Kingdom
² Div of Molecular Therapy, Institute of Opthalmology, London, United Kingdom
³ Developmental Biology Unit, Institute of Child Health, London, United Kingdom

Commercial Relationships: R.R. Ali, None; R.E. MacLaren, None; R.A. Pearson, None; A. MacNeil, None; J.C. Sowden, None.

Support: Medical Research Council

Abstract

Purpose: To determine if photoreceptor progenitor cells can migrate into the host outer nuclear layer (ONL), differentiate into photoreceptors and make synaptic connections in an adult mouse model of human retinitis pigmentosa.

Methods: Donor cells were isolated from retinae of post–natal transgenic mice expressing green fluorescent protein (GFP) and transplanted into the subretinal space of adult rds mice, which have no outer segments due to absence of the peripherin–2 gene.

Results: Three to ten weeks after transplantation, GFP photoreceptors were seen in the host ONL. Transplanted cells had spherule synapses, inner and outer segments (identified by peripherin–2 immunostaining) and functional photoreceptor–specific mGluR8 receptors. Transplantation of GFP cells into a transgenic mouse expressing blue fluorescent protein excluded cell fusion because green and blue fluorescent signals were not co–localised in the same photoreceptor. Transplantation was successful with a post–mitotic population of rod precursors, but could not be achieved with a mitotic population of embryonic retinal cells.

Conclusions: We provide novel evidence to show that immature post–mitotic retinal cells can be transplanted into an adult retina. These cells become fully–integrated, mature photoreceptors in a mouse model of human retinitis pigmentosa. Use of partly–differentiated stem cells may therefore be the best cell transplantation strategy for the treatment of retinal degenerations.

Keywords: photoreceptors • retinal degenerations: cell biology • retinal development

© 2006, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any part of this abstract, contact the ARVO Office at arvo{at}arvo.org.